Mental illnesses includes psychoses and neuroses. The symptoms requiring treatment include depression, anxiety, agitation and hallucinations. Drugs used particularly for treatment of both reactive and endogenous depressions include monoamine oxidase (MAO) inhibitors such as iproniazide, tranylcypromine, nialamide, phenelzine and paragyline and the non-MAO inhibiting tricyclic aromatic dibenzazepines such as imipramine and dibenzocycloheptadienes such as amitriptyline.
All of these drugs have side effects that limit their usefulness. The MAO inhibitors may cause tremors, insomnia, hyperhydrosis, agitation, hypermanic behavior, confusion, hallucinations, convulsions, orthostatic hypertension and death. They frequently cause dizziness, vertigo, headache, inhibition of ejaculation, difficulty in urination, weakness, fatigue, dry mouth, constipation and blurred vision. Imipramine may cause blurred vision, dryness of mouth, constipation, urinary retention, orthostatic hypotension, respiration depression, myocardial infarction and congestive heart failure. Similar difficulties are experienced with amitriptyline.
There is a genuine need for psychotherapeutic agents which are effective and have fewer side effects than the drugs in use today. The new and useful drugs disclosed here satisfy these criteria. They also have a beneficial tranquilizing action.
The compounds of this invention are cis- and trans-octahydropyridopyrrolobenzheterocycles. The compounds of the following patents can be reduced to form some of the novel compounds of this invention.
U.S. Pat. Nos. 3,914,421 and 4,013,652 disclose compounds of the formula: ##STR3## where the R's are the same or different and are H or CH.sub.3, and one of them can be C.sub.2 -C.sub.9 alkyl or phenyl;
R.sup.1 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.4 alkoxy-carbonyl, or substituted C.sub.1 -C.sub.4 alkyl where the substituent is the C.sub.3 -C.sub.6 cycloalkyl or phenyl; and Z is H, Cl or CH.sub.3 ; PA1 m and n are either 0 or 1 and the sum of m and n is at least 1; PA1 the R's are the same or different and are H or CH.sub.3, and one of them can be C.sub.2 -C.sub.9 alkyl, phenyl, C.sub.7 -C.sub.10 phenylalkyl, furyl, thienyl, pyridyl, phenyl or C.sub.7 -C.sub.10 phenylalkyl substituted on adjacent ring carbon atoms with methylenedioxy, or phenyl or C.sub.7 -C.sub.10 phenylalkyl substituted on the ring with 1, 2 or 3 substituents individually selected from methoxy, ethoxy, bromine, chlorine, fluorine, trifluoromethyl and C.sub.1 -C.sub.4 alkyl; when X is S and m is O, one R on the group --RCR-- can be --OCH.sub.3 ; and when X is S and m is 1, the R on the group (CHR).sub.m can be --OCH.sub.3 ; PA1 R.sup.1 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.3 -C.sub.5 alkenyl, C.sub.3 -C.sub.5 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.4 alkoxycarbonyl, trifluoroacetyl or substituted C.sub.1 -C.sub.4 alkyl where the substituent is C.sub.3 -C.sub.6 cycloalkyl, phenyl, phenyl substituted on adjacent carbon atoms with methylenedioxy, or phenyl substituted with 1, 2 or 3 substituents individually selected from methoxy, ethoxy, bromine, chlorine, fluorine, trifluoromethyl and C.sub.1 -C.sub.4 alkyl; and PA1 Z is H, Cl or CH.sub.3 ; PA1 m is 0 or 1; PA1 except that when X is O, the sum of n plus m is one or two; and when X is S, ##STR7## or SO.sub.2, n and m are both zero; the R's are the same or different and are H or CH.sub.3, and one of them can be C.sub.2 -C.sub.9 alkyl, phenyl, C.sub.7 -C.sub.10 phenylalkyl, furyl, thienyl, pyridyl, phenyl or C.sub.7 -C.sub.10 phenylalkyl substituted on adjacent ring carbon atoms with methylenedioxy, or phenyl or C.sub.7 -C.sub.10 phenylalkyl substituted on the ring with 1, 2 or 3 substituents individually selected from methoxy, ethoxy, bromine, chlorine, fluorine, trifluoromethyl and C.sub.1 -C.sub.4 alkyl; when X is S one R on the group --RCR-- can be --OCH.sub.3 ; PA1 R.sup.1 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.5 alkenyl, C.sub.3 -C.sub.5 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.4 alkoxycarbonyl, trifluoroacetyl or substituted C.sub.1 -C.sub.4 alkyl where the substituent is C.sub.3 -C.sub.6 cycloalkyl, phenyl, phenyl substituted on adjacent carbon atoms with methylenedioxy, or phenyl substituted with 1, 2 or 3 substituents individually selected from methoxy, ethoxy, bromine, chlorine, fluorine, trifluoromethyl and C.sub.1 -C.sub.4 alkyl; and PA1 Z is H, Cl or CH.sub.3 ; PA1 R.sub.2 =H, CH.sub.3, OCH.sub.3, Cl, Br, F or CF.sub.3. PA1 (1.) the configuration is cis; PA1 (2.) the cis configuration and a six-membered ring PA1 (3.) the cis configuration and a seven-membered ring wherein independently: PA1 (4.) the trans configuration wherein independently: PA1 (a.) a compound of the cis configuration wherein: PA1 (b.) a compound of the cis configuration wherein: PA1 (c.) the trans configuration wherein:
or its pharmaceutically suitable salts.
U.S. Pat. No. 4,115,577 discloses compounds of the formula: ##STR4## where X is S, S or SO.sub.2 ;
and their pharmaceutically suitable salts.
Copending U.S. patent application Ser. No. 916,846 filed June 16, 1978 by P. Rajagopalan (which is a continuation-in-part of U.S. patent application Ser. No. 263,766 filed June 9, l972 now abandoned) discloses a compound of the formula: ##STR5## where X is O, S, ##STR6## or SO.sub.2 ; n is 0 or 1;
and their pharmaceutically suitable salts.